Natural Selection Genomic Analysis

Natural Selection and its Correlation to Human Diseases Infections pathogens are the strongest forces that act against the human population. As migrations and cultural changes occurred in the past, individuals have become exposed to dangerous new pathogens. Host genetics influences resistance to infectious diseases and contributes to common diseases that show geographical disparities. An understanding of interaction between the host and the pathogen can inform the development of new medicines and therapies for those with infectious diseases. With the use of new “technologies, analytical method and expanding public data resources,” the investigation leads to new insights into the functions and dysfunctions of the human biology due to natural

The genomic analyses provide “insights into human evolution and implications for human health” (Karsson, Kwiatkowski, Sabeti 397). To test for signatures of selection, scans are made by statistical tools and by rapidly expanding the genome data sets in multiple human populations. The next-generation sequencing technologies enable generation of whole-genome sequence for analysis and it can detect all variation throughout one’s genome. Next, signatures of positive selection are tested based on the time of selection and whether the variant is standing or new. It can be found with three different signals - uncommonly large allele frequency differences in population, abnormally high frequencies of newly derived variants, and surprisingly extended LD that is caused by rapid increase of frequency from one allele. Cross-species

The long history of malaria complicates the test of resistance loci by GWAs. Because the LD is short and variable within populations, casual variants are inadequately tagged by SNP genotyping arrays. Leprosy was widespread in Europe and it rapidly declined after the 16th century. Today, it is a major health concern in India, China, and South America. The genetics differ between populations. The Indian cohort had strong association to the TLR1 gene that protects them against leprosy, which is completely absent in the Han Chinese population and in Indians, but extremely common in Europe. Tuberculosis affects 1/3 of the human population. It is said to have migrated from East Africa 40,000 years ago and have spread as ancient people migrated around the world. A GWAs of tuberculosis susceptibility only found 2 significant associations in a data set of 11 million SNP, and after replication, nearly 23,000 individuals. This shows that M. tuberculosis is more genetically diverse than M. leprae. The strongest signs of HIV resistance are found in the MHC loci; they are enormously positive and balancing selection. MHC variants offered an explanation for 19% of the phenotypic variance, which included a protective regulatory variant that is correlated with the expression of human leukocyte antigen. Individuals who are homozygous for null mutations of FUT2 gene do not secrete antigens and are protected against some